Changes within the thyroid axis after long-term TSH-suppressive levothyroxine therapy

Objective: The effects of long-term TSH-suppressive levothyroxine (LT4) therapy on thyroid hormone metabolism in patients with differentiated thyroid carcinoma (DTC) are unknown. The aim of the study was to investigate the changes in thyroid hormone metabolism after long-term TSH-suppressive LT4 therapy in patients with DTC. Patients and Methods: Sixty one patients with DTC were followed. For each patient, frozen remnant sera from two time points were selected: time1 (drawn within 1 year of I-131 ablation; TSH on file <0.3 mIU/l; recruitment period 1999-2002) and time2 (last available sample with TSH on file <0.3 mIU/l; minimum of 3 years of continuous TSH-suppressive LT4-therapy on record). TSH, reverse triiodothyronine (rT3), total triiodothyronine (TT3) and total thyroxine (TT4) levels were measured at both time1 and time2, and relationships between these parameters were analysed. Results: Total triiodothyronine, TT4 and TSH levels were significantly reduced at time2 (P < 0.001), whereas LT4 dose, bodyweight and rT3 levels remained constant between time1 and time2. There were no significant changes in the relationship between the dose of LT4/kg bodyweight and TT4 levels (P = 0.14). TT4/TT3 was increased at time2 (P < 0.001), whereas TT4/rT3 and TT3/rT3 were significantly decreased at time2. There appeared to be no relationship of the effects found and advancing age. Conclusion: After long-term TSH-suppressive LT4 therapy for DTC, there are significant changes in thyroid hormone metabolism, which are best explained by a combined downregulation of deiodinases subtypes 1 and 2 and an upregulation of deiodinase subtype 3.

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